Cilia in the brain

by wolfhnd on January 19th, 2018, 9:28 pm

Researchers are turning up roles for nerve cell cilia in a variety of brain functions. In a region of the brain linked to appetite, for example, cilia appear to play a role in preventing obesity, researchers report January 8 in three studies in Nature Genetics. Cilia perched on nerve cells may also contribute to brain development, nerve cell communication and possibly even learning and memory, other research suggests.

Re: Cilia in the brain

This is pretty cool. So the neurons are using these cilia like antenna's to chemo-sense their environment and transduce signaling pathways. I wonder why this specific structure evolved though, and what advantage it offers over receptors anchored directly into the cell membrane. Maybe it allows cells that don't have much exposure to interstitial space improved access to the molecular signals floating around. Very interesting concept and discovery, thanks for bringing it to my attention wolf.

The cilia may be a relatively recent example of symbiogenesis where the evolving nerve cells merged over time with an invading bacterium. This would bypass the difficulty of evolving receptors from the surface of the cell membrane.

Re: Cilia in the brain

Hi bangstorm. I think your hypothesis is creative. But why would evolving receptors here be any more difficult that the thousands of other receptors that cells have? I think the value that the cilia are adding here is increasing the the reach of the receptor(s) found on it. Especially for a cell that is crowded by other cells and can’t have enough access to the surrounding biochemical environment to sense it. Kind of like a submarine’s periscope.

Re: Cilia in the brain

BioWizard » January 21st, 2018, 4:50 pm wrote:Hi bangstorm. I think your hypothesis is creative. But why would evolving receptors here be any more difficult that the thousands of other receptors that cells have? I think the value that the cilia are adding here is increasing the the reach of the receptor(s) found on it. Especially for a cell that is crowded by other cells and can’t have enough access to the surrounding biochemical environment to sense it. Kind of like a submarine’s periscope.

It is my understanding that acquiring cilia by appropriating and adapting bacterial genomes is commonly the way cells acquire cilia in the first place. Guessing by the bacteria like morphology, the irregular distribution, and “perched on” appearance of the cilia, they appear to be a more like a something added on to the cell wall in a “recent” punctate evolution rather than a structure that evolved from within. Fine structures that have been acquired by symbiosis can be identified by having bits of DNA different from that of the nucleus and I suspect that sort of study will eventually be done.

Cellular evolution is limited to modification of existing structures and adding length to an existing structure is one of the easiest of modifications so I suspect a neuron cell would do just that if extending the length of a particular type of receptor were to prove beneficial. It is possible that the microbiome has evolved more efficient means of communication since the early evolution of the neuron cell so it would be easier for neuron cells to acquire the same means of communication from the environment by symbiosis rather than to evolve something similar de novo.

Re: Cilia in the brain

BioWizard » January 21st, 2018, 4:50 pm wrote:Hi bangstorm. I think your hypothesis is creative. But why would evolving receptors here be any more difficult that the thousands of other receptors that cells have? I think the value that the cilia are adding here is increasing the the reach of the receptor(s) found on it. Especially for a cell that is crowded by other cells and can’t have enough access to the surrounding biochemical environment to sense it. Kind of like a submarine’s periscope.

It is my understanding that acquiring cilia by appropriating and adapting bacterial genomes is commonly the way cells acquire cilia in the first place. Guessing by the bacteria like morphology, the irregular distribution, and “perched on” appearance of the cilia, they appear to be a more like a something added on to the cell wall in a “recent” punctate evolution rather than a structure that evolved from within. Fine structures that have been acquired by symbiosis can be identified by having bits of DNA different from that of the nucleus and I suspect that sort of study will eventually be done.

Cellular evolution is limited to modification of existing structures and adding length to an existing structure is one of the easiest of modifications so I suspect a neuron cell would do just that if extending the length of a particular type of receptor were to prove beneficial. It is possible that the microbiome has evolved more efficient means of communication since the early evolution of the neuron cell so it would be easier for neuron cells to acquire the same means of communication from the environment by symbiosis rather than to evolve something similar de novo.

Your theory may have merit but it points to the more important concept of seeing the brain as a colony of single cell organisms. On close examination pruning for example looks like survival in a competitive environment.

Re: Cilia in the brain

BioWizard » January 21st, 2018, 4:50 pm wrote:It is my understanding that acquiring cilia by appropriating and adapting bacterial genomes is commonly the way cells acquire cilia in the first place.

Yes, I'm not arguing that this is not a possibility. However, this idea has been much less accepted as the likely one. Cellular cilia are made of microtrubules and plasma membrane, which are not unique to the ciliary structure and are fundamental components of the cell's body. If you polymerize microtubles behind a plasma membrane, some are bound to poke out and form ciliary structures. So unlike the mitochondrion which has its own DNA and specific set of constituents, it seems to me that invoking endosymbiosis is superfluous for explaining the initial appearance of cellular cilia.

Guessing by the bacteria like morphology, the irregular distribution, and “perched on” appearance of the cilia, they appear to be a more like a something added on to the cell wall in a “recent” punctate evolution rather than a structure that evolved from within. Fine structures that have been acquired by symbiosis can be identified by having bits of DNA different from that of the nucleus and I suspect that sort of study will eventually be done.

There are only so many structures you can make with cytoskeletal elements and plasma membranes. Airplanes and dragonflies are have a lot of shared morphological features, but let's not speculate about shared ancestry there. A cytoskeletal structure poking out behind a plasma membrane is hardly enough to warrant this kind of speculation. Just think about how trivial the ciliary structure is compared to the much more complex and highly specialized processes that neurons extend (axons and dendrites).

Cellular evolution is limited to modification of existing structures and adding length to an existing structure is one of the easiest of modifications so I suspect a neuron cell would do just that if extending the length of a particular type of receptor were to prove beneficial. It is possible that the microbiome has evolved more efficient means of communication since the early evolution of the neuron cell so it would be easier for neuron cells to acquire the same means of communication from the environment by symbiosis rather than to evolve something similar de novo.

I don't know. But if these cilia exist in a lot of other cell types, I am less inclined to think that neuron's co-opting them for their own use marks a first-event in the evolutionary timeline.

Re: Cilia in the brain

If you notice, the axon is like a giant cilium, and the entire nervous system is kind of like a central body with stringy appendages coming off it. That central body is isolated from the rest of the body by the blood/brain barrier. It has its own immune system. The little cilia appear to be part of a theme.

Re: Cilia in the brain

Asparagus » 22 Jan 2018 03:11 pm wrote:If you notice, the axon is like a giant cilium, and the entire nervous system is kind of like a central body with stringy appendages coming off it. That central body is isolated from the rest of the body by the blood/brain barrier. It has its own immune system. The little cilia appear to be part of a theme.

Asparagus, I think you said it a lot better and more concisely than I did.

Re: Cilia in the brain

BioWizard » January 22nd, 2018, 2:24 pm wrote:Yes, I'm not arguing that this is not a possibility. However, this idea has been much less accepted as the likely one. Cellular cilia are made of microtrubules and plasma membrane, which are not unique to the ciliary structure and are fundamental components of the cell's body.

Yes, that appears to be the case. I did some looking into the evolutionary origin of cilia and the general consensus is that cilia evolved from microtubules on the surface of eukaryotic cells rather by symbiogenesis with bacteria.

“Eukaryotic cilia and flagella are motile organelles built on a scaffold of doublet microtubules and powered by dynein ATPase motors. Some thirty years ago, two competing views were presented to explain how the complex machinery of these motile organelles had evolved. Overwhelming evidence now refutes the hypothesis that they are the modified remnants of symbiotic spirochaete-like prokaryotes, and supports the hypothesis that they arose from a simpler cytoplasmic microtubule-based intracellular transport system. However, because intermediate stages in flagellar evolution have not been found in living eukaryotes, a clear understanding of their early evolution has been elusive.”

The intermediate stages of flagellar evolution in bacteria have since been identified along with the accompanying changes in bacterial DNA and their origin has been traced back to the tubular structures on the surface of bacteria known as pili. Prior to this discovery, the evolution of flagella had been a thorny problem to explain ever since it was discovered that flagella can continuously rotate through 360 degrees so flagella function more like motor driven propellers than like tails devoted to swimming. This was against the long held notion that evolution could never produce a wheel.

Re: Cilia in the brain

The longer I’m in this forum the more I realise how ignorant I am, and the more I wonder how much is yet to be discovered. I’d never heard of these cilia on neurons nor of the Arc gene protein vesicles discussed in another thread – thanks to Wolfhnd and Zetrique respectively.

Whilst perusing this thread I was tending to agree with Biowizard, who said in one post – “Especially for a cell that is crowded by other cells and can’t have enough access to the surrounding biochemical environment to sense it. Kind of like a submarine’s periscope”, and in a later post – “I don't know. But if these cilia exist in a lot of other cell types, I am less inclined to think that neuron's co-opting them for their own use marks a first-event in the evolutionary timeline”, and of Asparagus who said – “That central body is isolated from the rest of the body by the blood/brain barrier. It has its own immune system. The little cilia appear to be part of a theme.”

And Bangstrom, I see where you have changed from your position of their origin being a result of symbiogenesis with bacteria. It was because of that position I did some research this arvo.I may as well post it anyhow.

My impression is that these cilia have been around for quite a long time on the evolutionary scale. A couple of these references suggest that their absence results in the loss of some vital functions. If they were just ‘recently’-acquired appendages from an evolutionary point of view, one would expect that their absence would not have such marked effects.

The author (Laura Sanders) of the Science News article that was posted in the OP, cited the first three of the following.

1. Mice without normal cilia in parts of their brain had trouble remembering a painful shock and recognizing familiar objects - http://journals.plos.org/plosone/articl ... ne.0106576 . The title of the paper was Hippocampal and Cortical Primary Cilia Are Required for Aversive Memory in Mice (by Malarky et al) - “we specifically disrupted ciliogenesis in the cortex and hippocampus of mice through conditional deletion of the Intraflagellar Transport 88 (Ift88) gene. The effects on learning and memory were analyzed using both Morris Water Maze and fear conditioning paradigms. In comparison to wild type controls, cilia mutants displayed deficits in aversive learning and memory and novel object recognition.” These seem to me to be important survival requirements for mammals at least.

2. "Impaired signalling from the primary cilia of MC4R neurons is a common pathway underlying genetic causes of obesity of humans. The authors demonstrated that MC4R colocalises with adenylyl cyclase 3 (ADCY3) at the primary cilia of a subset of hypothalamic neurons, that obesity-associated MC4R mutations impair ciliary localisation and that impairment of adenylyl cyclase signalling at the primary cilia of these neurons increases body weight - http://www.nature.com/articles/s41588-0 ... cenews.org This article was presented as a PDF; I couldn't copy and paste so retyped the above part Abstract.

3. In an article titled C. elegans Ciliated Sensory Neurons Release Extracellular Vesicles that Function in Animal Communication by Wang et al – see https://www.sciencedirect.com/science/a ... 2214000037 - the authors made certain claims as shown in this part of their summary - “We show here that specific Caenorhabdidits elegans ciliated sensory neurons shed and release extracellular vesicles (ECVs) containing GFP-tagged polycystins LOV-1 and PKD-2. These ECVs are also abundant in the lumen surrounding the cilium. Electron tomography and genetic analysis indicate that ECV biogenesis occurs via budding from the plasma membrane at the ciliary base and not via fusion of multivesicular bodies. Intraflagellar transport and kinesin-3 KLP-6 are required for environmental release of PKD-2::GFP-containing ECVs. ECVs isolated from wild-type animals induce male tail-chasing behavior, while ECVs isolated from klp-6 animals and lacking PKD-2::GFP do not. We conclude that environmentally released ECVs play a role in animal communication and mating-related behaviors.”

You’ll note that the first two studies involve hippocampus and hypothalamus neurons, the former being involved in emotional responses, and the latter with the autonomic nervous system.

4. This article - http://www.sciencedirect.com/science/ar ... 6803002419 - The neuronal primary cilium—an extrasynaptic signaling device by JF Whitfield, indicates that these cilia are also present on retinal rods and cones as well as on kidney cells. The fact that their disablement causes polycystic kidney disease indicates that they have a vital rather than minor function. Abstract"Many, but likely most, neurons in the central nervous system have a nonmotile “primary” cilium extending like an antenna or finger from one of the pair of centrioles in the cell's centrosome into the extracellular space. Since their discovery over 100 years ago, these organelles have been either dismissed as functionless relicts of a bygone era or more often simply ignored. However, it has long been known that the photoreceptor-bearing outer segments of retinal rods and cones are modified primary cilia and it has recently been found that kidney cells' primary cilia are sensitive flowmeters the disabling of which causes polycystic kidney disease. It has also been recently shown that somatostatin sst3 receptors and serotonin 5-HT6 receptors are selectively sited on neurons in various parts of the rat brain. It seems likely that these selectively-receptored neuronal primary cilia will turn out to be the forerunners of a family of cell-signaling devices that help drive various brain functions by sending signals into their own cells and into adjacent cells through gap junctions and via conventional chemical synapses."

In view of the nature of the effects of interfering with the function of these cilia, I imagine that they have been around virtually since the origins of specialised cells. The serious studies on them seem to be relatively recent.